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Differential genetic susceptibility in diphasic and peak-dose dyskinesias in Parkinson's disease

Authors

  • Jee-Young Lee MD,

    1. Department of Neurology, Seoul National University Boramae Hospital, Seoul, Korea
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  • Jinwhan Cho MD, PhD,

    1. Department of Neurology, Samsung Medical Center, Seoul, Korea
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  • Eun-Kyung Lee RN,

    1. Department of Neurology, Seoul National University Hospital, Seoul, Korea
    2. Clinical Research Institute and Movement Disorders Center, Parkinson Disease Study Group, Seoul National University Hospital, Seoul, Korea
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  • Sung-Sup Park MD, PhD,

    1. Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea
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  • Beom S. Jeon MD, PhD

    Corresponding author
    1. Department of Neurology, Seoul National University Hospital, Seoul, Korea
    2. Clinical Research Institute and Movement Disorders Center, Parkinson Disease Study Group, Seoul National University Hospital, Seoul, Korea
    3. Neuroscience Research Institute, College of Medicine, Seoul National University, Seoul, Korea
    • BK21, Neuroscience Research Institute, Seoul National University College of Medicine, Department of Neurology, Clinical Research Institute and Movement Disorders Center, Seoul National University Hospital, Seoul 110-744, Korea
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  • Potential conflict of interest: This study was supported by a grant of the Seoul National University Hospital and the Korea Health 21 R&D Project, Ministry of Health, Welfare and Family, R.O.K. (A030001). The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. There is no conflict of interest.

Abstract

To examine whether there is a differential genetic susceptibility in the diphasic and peak-dose forms of levodopa-induced dyskinesias (LID) in patients with Parkinson's disease (PD). The study cohort comprised 503 unrelated Korean PD patients who were treated with levodopa and had a disease duration of at least 5 years. The presence of LID was identified during a routine follow-up and special care was taken to separate the two distinct forms of LID into diphasic and peak-dose dyskinesias (PDSK). Genotyping was performed in the 503 patients and in 559 healthy controls to search for polymorphisms of DRD3 p.S9G, DRD2 Taq1A, GRIN2B c.2664C>T, c.366C>G, c.-200T>G, and the promoter region of SLC6A4. A total of 229 patients expressed LID (peak-dose in 205, diphasic in 57, and both in 33). The presence of diphasic dyskinesia (DDSK) was exclusively associated with the DRD3 p.S9G variant after adjusting for gender, age at PD onset, Hoehn & Yahr stage, and duration of levodopa treatment. Carrying the AA genotype was likely to shorten the onset of DDSK according to the duration of levodopa therapy (P = 0.02). The presence of PDSK was not significantly associated with any of the six genetic variants studied. There may be a genetic susceptibility in the development of DDSK in PD patients on chronic levodopa therapy, and its underlying pathophysiological mechanism might be distinct from that of PDSK. © 2010 Movement Disorder Society

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